Nutritional Management of Crohn’s Disease

Note: This was a research paper for my Vitamins & Minerals graduate class. I made a few additions since turning in the paper, but I believe the conclusions about the best diet for Crohn’s disease apply to everyone with an autoimmune disease, inflammatory disease, or gastrointestinal issues.

Nutritional Management of Crohn’s Disease


Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) caused by a complex interplay between genetics and environment. This paper looks at a few of the most common underlying factors of CD including several genetic mutations that cause innate and adaptive immune system dysfunction, microbiota changes associated with the disease, and dietary risk factors. It also investigates successful adjunct treatments including diet and nutrition that reduces disease activity and treats or prevents nutritional deficiencies common in CD.


CD is a relapsing and remitting autoimmune disease that primarily affects the gastrointestinal tract (Baumgart & Sandborn, 2012). Risk of developing CD varies from less than 1 to 16/100,000 people, while prevalence of the disease is estimated at 70-200/100,000 people (Hart & Ng, 2015). Currently North America and Northern and Western Europe have the highest rates, while South America, Africa, and Asia have the lowest (Hart & Ng, 2015). The number of people diagnosed with CD, however, has been increasing, particularly among children under 10 years old and in non-Western cultures (Hart & Ng, 2015).

Risk Factors

Risk factors for CD include family history of IBD, smoking or sustained exposure to second-hand smoke, NSAID use, and gastroenteritis (Baumgart & Sandborn, 2012). Other factors associated with the development of CD include high consumption of monosaccharides like glucose and fructose, trans fatty acids from partially hydrogenated vegetable oils, and omega-6 fatty acids in vegetable oils and diets low in fiber, fruits, vegetables, and omega-3 fatty acids (Owczarek, Rodacki, Domagała-Rodacka, Cibor, & Mach, 2016). Since diet is one of the associated risks of developing CD, there is a high probability that increased global trade in highly processed foods that contain refined sugars and vegetable oils is increasing the prevalence of the disease in cultures that once depended on traditional whole foods diets.

Signs & Symptoms

CD can occur in any part of the gastrointestinal tract, though it is most often found in both the ileum and colon, the ileum alone, or the colon alone (Hart & Ng, 2015). Inflammation and lesions in the mucosal and/or epithelial layers of the intestine tend to be disconnected rather than continuous and can vary in size and depth (Hart & Ng, 2015). If the lesions burrow deep enough, fistulas can form from the affected intestine to other organs including the bladder, skin, or adjoining section of intestine (Hart & Ng, 2015). Symptoms of CD can include blood and/or mucus in the stool, stomach cramps or intestinal pain, urinary incontinence, diarrhea, weight loss, and fatigue (Baumgart & Sandborn, 2012). Twenty-five to forty percent of those with CD develop extraintestinal manifestations (EIM), including musculoskeletal diseases like arthritis, ankylosing spondylitis, and osteoporosis; skin and oral problems like mouth ulcers, lesions or necrotic ulcerations, fissures or fistulas, and psoriasis; eye problems like uveitis, scleromalacia, and corneal ulcers; and hepato-pancreato-biliary diseases like bile duct inflammation and scarring, autoimmune hepatitis, cirrhosis, granulomatous disease, and fatty liver disease (Levine & Burakoff, 2011).

Diagnosis & Treatment

Diagnosis of CD is usually made after laboratory tests of blood and stool, an endoscopy along with multiple biopsies, and imaging tests such as CT or MRI (Baumgart & Sandborn, 2012). Histological signs of CD include pervasive submucosal inflammation, patches of chronic inflammation, and granulomata (Hart & Ng, 2015). A detailed medical history and thorough physical exam should also be done to identify risk factors and check for extraintestinal signs of disease. Diagnosis should not be made based on a single testing method but on the accumulation of medical data.

Conventional medical treatment of CD include medications to suppress the immune system, usually corticosteroids or tumor necrosis factor (TNF) blocking drugs (biologics) are prescribed short term to slow down progression of the disease along with thiopurine drugs, immunomodulators, or methotrexate for long term maintenance (Baumgart & Sandborn, 2012). Too often corticosteroids are prescribed long term, increasing risks of serious side-effects, including bone loss and osteoporosis. Life threatening infections, especially Clostridium difficile, are a concern with drugs that suppress the immune system. Surgeries to repair fistulas or remove segments of diseased intestine should be done judiciously (Hart & Ng, 2015).

There are several alternative or adjunct therapies for CD under investigation. Fecal transplants that colonize the intestines with a healthy community of microbiota have shown some success at remission of CD, but large clinical trials have not been done (Hart & Ng, 2015). Small trials of low dose naltrexone, an opiate antagonist with immune system modulation properties, showed some improvement of CD with the drug, but trials were very small and results were inconsistent (Segal, Macdonald, & Chande, 2014). A trial of medical marijuana in patients who had poor response to standard treatment showed clinically significant improvement in CD disease activity in the treatment group compared to placebo group, but again it was a small trial with little data to extrapolate to a larger population of CD patients (Naftali, et. al., 2013).


Susceptibility to CD is genetic and it is thought to be triggered by environmental factors that disturb the natural balance of the microbiota in the gut and disrupt the normal functions of the innate and adaptive immune systems (Baumgart & Sandborn, 2012). Genetic polymorphisms in NOD2, ATG16L1, and IRGM have been strongly associated with the development of CD (Hart & Ng, 2015). All three genes are involved in immune system pathways that respond to microbes and autophagy, the destruction and elimination of cellular material, within intestinal epithelial cells (Billmann-Born, et. al. 2011).

NOD2 is involved in the recognition and protection of the body from certain species of pathogens through its expression in innate immune cells (Billmann-Born, et. al. 2011). Disruption of NOD2 activity due to genetic polymorphisms corrupts the immune system’s natural ability to ignore commensal bacteria and fight pathogens resulting in less tolerance to pathogens and hyperactive immune responses from B cells (Hart & Ng, 2015). NOD2 also interacts with enzymes that synthesize reactive oxygen species (ROS); increased ROS activity can cause cellular damage associated with chronic inflammatory diseases (Billmann-Born, et. al. 2011). Since NOD2 modulates nuclear factor-κB (NFκB), a transcription factor that controls cytokine production, regulation of pro-inflammatory cytokines tumor necrosis factor- α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) are disrupted by this gene mutation increasing systemic inflammation as well as intestinal inflammation (Hart & Ng, 2015).

Autophagy in a multi-stage process for isolating, recycling, and eliminating damaged or excess cellular material and intracellular microbes. Autophagy is important for proper innate immune response and also plays a role in adaptive response through antigen presentation in major histocompatibility complex (MHC) class II (Palomino-Morales, et. al., 2009). ATG16L1 is involved in the first step of the autophagy process, the formation of membranes around cellular material (Billmann-Born, et. al. 2011). Altered ATG16L1 results in a disruption in pathogen destruction and antigen processing which causes reduced protection against microbes and protracted immune system activation increasing pro-inflammatory cytokines IL-1β, IL-18, TNF-α, and interferon- γ (IFN-γ) (Palomino-Morales, et. al., 2009). Mutations in the IRGM gene induces inappropriate autophagy against intracellular bacteria resulting in increased destruction of commensal bacteria that protect against pathogenic microbes (Palomino-Morales, et. al., 2009). IRGM haplotypes have been identified that increase risk of developing CD and that are protective against developing the disease (Palomino-Morales, et. al., 2009). Anti-inflammatory T helper 2 (TH2) cytokines IL-4 and IL-13 are regulated by IRGM and dysregulation of them is suspected to be one of the reasons for the autoimmunity found in CD (Hart & Ng, 2015).


There are an estimated hundred trillion microbial organisms residing in the human intestinal tract that affect everything from immune function, metabolism, nutrition, and physiology (Guinane & Cotter, 2013). This microbiota contains thousands of diverse species and disruption of this microbial community (dysbiosis) can have a huge impact on human health; diseases associated with dysbiosis include obesity, malnutrition, diabetes, and IBDs like CD (Guinane & Cotter, 2013). Intestinal inflammation seen in CD is associated with a reduction in microbial diversity and several studies have linked mucosal lesions seen in CD with intestinal microbes, particularly an overabundance of adhesive E. coli (Guinane & Cotter, 2013). Dysbiosis with an increase in adhesive mucosal bacteria has been observed in patients who developed CD after gastroenteritis (Baumgart & Sandborn, 2012). While other causalities have not been established between dysbiosis and CD, a number of phyla and species of microbes have been identified that are reduced or increased in patients with CD compared with healthy controls (Guinane & Cotter, 2013). Manipulation of the microbiota through diet, prebiotics, probiotics, fecal transplants, antimicrobials, or antibiotics have been employed as adjunct treatment for CD. Results have been mixed, with probiotic therapies showing little to no improvement in disease activity (Owczarek, et. al., 2016).


Those with CD are at risk for developing nutritional deficiencies due to intestinal inflammation or lesions, medications used to treat the disease, and other factors like small intestine resections and decreased food intake which impact the digestion and absorption of nutrients. The most common deficiencies are: iron, calcium, vitamin D, vitamin K, vitamin B12 and folate but other deficiencies or sub-optimal levels can occur (Owczarek, et al., 2016). Assessment of nutritional status should include a dietary intake history, physical exam, body composition exam, and anthropometry along with in depth nutritional testing and a medical history. Knowledge of disease activity and active sites of inflammation in the intestinal tract helps with the design of an individualized treatment plan. For example, iron absorption occurs in the duodenum and ileum while vitamin B12 absorption takes place in the ileum. Active disease sites in these areas can greatly affect nutritional status.


Ideally adequate nutrition for those with CD can be obtained from a diet low in inflammatory foods and high in anti-inflammatory foods. A number of specialized diets have been investigated for the treatment of CD, including the Mediterranean Diet, Specific Carbohydrate Diet (SCD), low FODMAP, vegetarian diets, ancestral or paleolithic diets, and anti-inflammatory diets, all with various levels of success (Owczarek, et. al., 2016). SCD appears to be the most successful and the most studied when it comes to the dietary treatment of children with CD, but clinical trials of specialized diets are small and adherence to many of the diets are difficult (Burgis, Nguyen, Park, & Cox, 2016). Instead of recommending a specific specialized diet for patients with CD, effort should be made to individualize a diet that takes into consideration the patient’s unique needs while increasing anti-inflammatory foods and reducing inflammatory foods. Diets that reduce inflammation in general are whole foods based with low intake of highly processed foods, refined grains, simple sugars, omega-6 fatty acids, and alcohol and high intake of vegetables, fruits, fatty fish and other nutrient dense proteins, natural monounsaturated and omega-3 fatty acids, natural fiber from food sources, and plant polyphenols from tea, cocoa, and berries (Wu & Schauss, 2012). Grains, if eaten, should be intact or cracked rather than milled. Mucosal healing and reduction in inflammation should be the goal of any diet used to as adjunct treatment of CD; whole foods diets rich in vegetables and fruits and that contain minimal processed foods can achieve both (Whalen, et. al., 2016). There’s evidence that a whole foods diet can change and improve intestinal dysbiosis common in CD, as well as change gene expression to reduce pro-inflammatory cytokines (Marlow, et. al., 2013).

Meal Replacement

Depending on symptoms and disease status, adequate nutrition from whole foods is not always possible. While parenteral nutrition (PN) was once thought to help CD patients with active disease obtain remission, the risks of complications with intravenous nutrition are great and it is now seldom used (Hartman, Eliakim, & Shamir, 2009). Enteral nutrition (EN) has shown to be much more successful at improving nutritional status, decreasing inflammatory biomarkers, healing the mucosal lining, and inducing remission (Hartman, Eliakim, & Shamir, 2009). EN can be obtained through elemental or polymeric meal replacement formulas (Hartman, Eliakim, & Shamir, 2009). In rare cases EN formulas can be given though a feeding tube. If EN is given exclusively, effort should be made to transition patients back to eating whole foods as all or part of the diet once the mucosal lining has healed in one to two months (Owczarek, et. al., 2016).

Some studies recommend 35-50% of total calories per day (approximately 600 calories) be obtained through EN formulas to maintain remission in patients with CD (Owczarek, et al., 2016). Considering many CD patients eliminate foods they believe worsens their symptoms or can not eat adequate amounts of food to maintain energy or nutrition, supplementing with EN formulas should be seriously considered on a case by case basis.


Patients who can not get adequate nutrition from foods may also need supplementation of key nutrients. Iron deficiency occurs in more than 60% of CD patients due to inflammation and low dietary intake (Owczarek, et al., 2016). Symptoms of iron deficiency include fatigue, dizziness, tingling in hands and feet, and shortness of breath. Due to the side-effects and the risk of increasing disease activity in the intestines, intravenous iron infusions should be given to CD patients with active disease or poor tolerance to oral iron supplements (Stein & Dignass, 2013). Iron isomaltoside at 1000mg and Ferric carboxymaltose at 1000mg or less are fast infusing and appear to correct anemia better than some of the other IV iron formulas, though both require maintenance doses at different intervals (Stein & Dignass, 2013). For oral supplementation, ferrous sulfate at 325mg (65mg elemental iron) three times a day is suggested until deficiency is resolved; lower doses may decrease side-effects but also prolong deficiency (Alleyne, Horne, & Miller, 2008). Adding low dose vitamin C supplement (125-250 mg) along with the iron supplement will increase absorption, as will taking it on an empty stomach; coffee, tea, high fiber meals, and taking iron with other minerals will decrease absorption (Alleyne, Horne, & Miller, 2008).

Patients with CD are at increased risk of developing osteoporosis, especially those on long term corticosteroid therapy. Supplementation with calcium, vitamin D, and vitamin K may be required to correct and prevent deficiencies and maintain bone health. Adequate intake of calcium should be between 1000-1500 mg/day (Owczarek, et al., 2016). If this can not be achieved in diet, then supplementation is recommended. 400-500 mg/day of calcium citrate taken once or twice a day along with vitamin D is suggested. Hypercalcemia can occur if calcium is not absorbed and eliminated properly or intake is too high. Symptoms of hypercalcemia include fatigue, confusion, excessive thirst, frequent urination, muscle pain and weakness. Inflammation biomarkers C-reactive protein (CRP), IL-6, and TNF-α decrease in patients with CD when vitamin D levels are optimal (Owczarek, et al., 2016). Supplementation of 2000-5000 IU/day of vitamin Dis recommended, depending on levels and sun exposure. Vitamin D toxicity also causes hypercalcemia. Vitamin K is often low in patients with CD and it is required for proper bone remolding and blood clotting. Vitamin K is synthesized by bacteria in the colon, so active disease states, inflammation, or dysbiosis can affect vitamin K levels. Supplementation of vitamin K1 does not produce measurable changes in bone health in patients with CD (O’Connor, et. al. 2014). However, supplementation of vitamin K2 at 45-100 mg/day improves bone turnover in patients with autoimmune disease on corticosteroids (Shikano, et. al., 2016).

Vitamin B12 is often deficient in patients with CD, particularly if there is active inflammation in the ileum. 5-40 mcg of an 1000-2000 mcg/day oral supplement can be absorbed by passive diffusion; normalization of vitamin B12 and MMA levels occurs after 3-4 months of treatment (Battat, et. al., 2014). Monthly intramuscular injections (IM) should be considered if neurological symptoms of deficiency do not improve with oral treatment. Folate is also a common B vitamin deficiency in those with CD, particularly in those taking the drug sulphasalazin (Owczarek, et al., 2016). Supplementation of 400 mcg/day of methylfolate is suggested to prevent deficiency with higher doses recommended only under medical supervision to correct anemia. Folic acid toxicity can mask B12 deficiency so methylfolate is recommended.

Increased intake of foods containing magnesium, zinc, and vitamin A or vitamin A precursors like β-carotene should be encouraged. Supplementation of these nutrients are only necessary if deficiencies occur (Owczarek, et al., 2016). Because of the gasterointestinal side-effects of magnesium, immune system side-effects of zinc supplementation, and risk of toxicity with vitamin A supplements, food is the best source of these nutrients. Best food sources of magnesium include: leafy greens, nuts and seeds, cold water fatty fish, legumes, and avocados. Shellfish, red meat, poultry, nuts and seeds, cheese, and cooked leafy greens are good sources of zinc. Vitamin A and its precursors are found in organ meats, cold water fatty fish, and orange colored vegetables or fruits like yams, cooked carrots, butternut squash, and dried apricots as well as in cooked leafy greens. Because vitamin A is a fat soluble vitamin, plant sources of vitamin A precursors should be eaten with good fats like the omega-3 fatty acids contained in unheated cold-pressed flaxseed oil, cold-pressed hemp seed oil and cold-pressed extra virgin olive oil or that are in organic, grass fed butter or whole milk yogurt.


CD is a complex gastrointestinal disease that involves genetic mutations as well as environmental factors that cause systemic and localized inflammation. Management of CD should involve nutrition as well as conventional medical treatments in order to modulate the immune system, reduce inflammation, decrease disease activity, improve symptoms, and prevent nutritional deficiencies. Lifestyle changes that include smoking cessation and stress reduction should also be discussed. A whole foods diet that reduces highly processed foods and includes greater quantities of vegetables, fruits, and omega-3 fatty acids is highly recommended. Supplemental nutrition, especially during periods of disease activity, is encouraged. That can include vitamin or mineral supplementation as well as meal replacement formulas depending on the patient’s specific needs. While diet, nutrition, and lifestyle changes alone likely will not cause remission of CD, when combined with other treatments, remission and reduction of recurrences of active disease states should be possible.


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